Brain function discovery helps explain why childhood adversity raises metabolic disease risk in women

McGill University researchers have identified a brain function that helps explain why childhood stress raises metabolic health risks for some women later in life.

A new study found that variations in the brain's insulin receptor network affect how women respond to early-life adversity. This effect has a lesser impact in men, suggesting there is a sex-specific process at play.

The findings, published in Communications Biology (Nature Portfolio), point to the brain's insulin receptor network as a promising avenue for earlier detection and future prevention strategies for metabolic syndrome, a major driver of cardiovascular disease that affects about one in five Canadian adults.

We know that women who face childhood adversity are at higher risk for metabolic disease, and this study helps identify who is most susceptible."

Dr. Patricia Pelufo Silveira, senior author, professor of psychiatry at McGill and researcher at the Douglas Research Centre

Why some women are at higher risk

Metabolic syndrome is a mix of factors, such as high blood pressure, high blood sugar, elevated triglycerides, elevated unhealthy cholesterol and excess abdominal fat that raise the risk of diabetes and cardiovascular diseases.

Analyzing data from more than 32,000 adults, the researchers found that among women who experienced early adversity, only those with a particular pattern of brain-insulin function showed increased abdominal fat and higher metabolic syndrome risk.

Everyone has a brain-insulin function that varies from person to person and appears to be a built-in feature of the brain, rather than something shaped by stress, the researchers note.

"We're not just talking about severe trauma. Common stresses such as being born with low birth weight, family conflict and physical or emotional neglect also matter," said first author Angela Marcela Jaramillo-Ospina, a postdoctoral fellow at McGill.

"If we can identify biological sensitivity early, we can intervene before these experiences translate into disease later in life," she said.

Measuring insulin in the brain

Insulin, well known for regulating blood sugar, also plays a major role in cognition and behaviour. Since insulin can't be easily measured directly in the brain, the researchers developed a method that uses DNA to find an estimate.

The method was validated by Jaramillo-Ospina in earlier research, which found that children with a similar brain-insulin receptor function and early stress were more likely to crave foods high in sugar and fat, which can set the stage for later metabolic problems.

What's still unclear is how the brain–insulin pathway regulates metabolic risk and why only some women are sensitive to it. The team plans to trace these signals in future research.

About the study

"Brain insulin receptor gene network shapes risk for metabolic disease after early-life stress in women" by Angela Marcela Jaramillo-Ospina and Patricia Pelufo Silveira et al., was published in Communications Biology.

This research was supported by the Canadian Institutes of Health Research, the JPB Foundation, McGill's Healthy Brains, Healthy Lives initiative and the McGill-Douglas Max Planck Institute of Psychiatry International Collaborative Initiative in Adversity and Mental Health.